MAPT and Alzheimer disease: Moreover, in AD pathogenesis, insulin-like growth factor 1 (IGF-1) that acts as a regulator of tau phosphorylation is silenced in activated astrocytes by Aβ/calcineurin-induced release of IGF-1-binding protein 3 (IGFBP-3); but intriguingly, Aβ directly induces increases in tau phosphorylation, and resulting neuronal death, via a mechanism involving the silencing of NFAT export kinase GSK-3β [195], suggesting opposite roles for calcineurin in AD pathogenesis.